Pseudoephedrine or a pharmaceutically acceptable salt thereof, e.g., pseudoephedrine sulfate, has been recognized by those skilled in the art as a sympathomimetic drug effective for treating nasal congestion. Loratadine, a non-sedating antihistaminic agent, is also known to be useful as an anti-allergy agent for the treatment of seasonal allergic rhinitis symptoms such as sneezing and itching. Therefore, an oral dosage composition containing both loratadine and pseudoephedrine or a pharmaceutically acceptable salt thereof is useful for treating patients showing the sign and symptoms associated with upper respiratory diseases and allergic rhinitis (see U.S. Pat. No. 5,314,697)
However, the biological half-life of pseudoephedrine sulfate is only about 6.3 hours, while loratadine, which combines with plasma proteins after being absorbed through the gastrointestinal tract, has a much longer biological half life of 12 to 15 hours. Further, loratadine has a poor water-solubility and exhibits a very low dissolution rate. Therefore, a conventional formulation prepared by simply mixing loratadine and pseudoephedrine or its salts is not capable of maintaining therapeutically effective blood concentrations of both ingredients at the same time for a prescribed period.
In order to solve the above problem, U.S. Pat. No. 5,314,697 suggests a film-coated tablet comprising an extended-release matrix core containing pseudoephedrine sulfate and a hydrophilic gel, a coating layer containing loratadine being formed on said core. When this formulation is ingested, loratadine having a longer biological half-life is released from the coating layer before the dissolution of pseudoephedrine sulfate having a shorter biological half-life from the extended-release matrix core.
However, the solubility and dissolution rate of loratadine from the outer layer decrease markedly in a high pH environment, and for this reason, the dissolution of pseudoephedrine sulfate from the extended-release matrix core may be unduly delayed. That is, the dissolution of pseudoephedrine sulfate is highly affected by the degree of wetting and dissolution of loratadine in the outer layer, and therefore, the release profile of pseudoephedrine sulfate fluctuates in an unpredictable manner with the pH of the gastrointestinal fluid which varies widely depending on various factors such as the amount and kind of ingested food.
Further, U.S. Pat. No. 5,807,579 discloses a tablet composition comprising extended-release pellets containing pseudoephedrine or its salts that are dispersed in a matrix containing an antihistaminic agent and optional pseudoephedrine or its salts. However, this composition also suffers from the problem of poor wetting of loratadine at a high pH condition, which may lead to an unsatisfactory mode of pseudoephedrine delivery.
The present inventors have carried out extensive research to solve the aforementioned problems; and, have discovered that a pharmaceutical capsule composition, which comprises rapid-release pellets containing loratadine and pseudoephedrine or a salt thereof, and extended-release pellets containing pseudoephedrine or a salt thereof, which are coated with a water-insoluble polymer and a wet-blocking agent, are free of above problems and exhibit controllable, satisfactory release profiles of both ingredients.